• Clayton T Bauer, Matthew L Banks, and S Stevens Negus.
• Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 N. 12th St., PO Box 980613, Richmond, VA, 23298, USA.
• Psychopharmacology (Berl.). 2014 Jun 1; 231 (12): 2461-70.

RationaleChronic amphetamine treatment reduces cocaine self-administration in pre-clinical and clinical settings, and amphetamine has been proposed as a candidate medication for treatment of cocaine abuse.ObjectiveThe objective of the present study was to investigate whether chronic amphetamine treatment can decrease abuse-related cocaine effects in an assay of intracranial self-stimulation (ICSS).MethodsThirteen adult male Sprague-Dawley rats were equipped with intracranial electrodes targeting the medial forebrain bundle and trained to lever press for pulses of brain stimulation in a "frequency-rate" ICSS procedure. Cocaine (10 mg/kg) was administered before (day 0), during (days 7 and 14), and after (posttreatment days 1 and 3) 2 weeks of continuous treatment with either amphetamine (0.32 mg/kg/h, n = 7) or saline (n = 6) via osmotic pump.ResultsPrior to treatment, cocaine facilitated ICSS in all rats. Saline treatment had no effect on baseline ICSS or cocaine-induced facilitation of ICSS at any time. Conversely, amphetamine produced a sustained though submaximal facilitation of baseline ICSS, and cocaine produced little additional facilitation of ICSS during amphetamine treatment. Termination of amphetamine treatment produced a depression of baseline ICSS and recovery of cocaine-induced facilitation of ICSS.ConclusionsThese data suggest that chronic amphetamine treatment blunts expression of abuse-related cocaine effects on ICSS in rats.

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